Structural basis for high-order complex of SARNP and DDX39B to facilitate mRNP assembly

作者：Yihu Xie, Shengyan Gao, Ke Zhang, Prasanna Bhat, Bradley P. Clarke, Kimberly Batten, Menghan Mei, Matthew R. Gazzara, Jerry W. Shay, Kristen W. Lynch, Alexia E Angelos, Pate S. Hill, Austin L. Ivey, Beatriz M. A. Fontoura, Yi Ren · 发表于：Cell Reports · 年份：2023 · DOI：10.1016/j.celrep.2023.112988 · 被引用次数：31 · 研究领域：RNA Research and Splicing、RNA modifications and cancer、RNA and protein synthesis mechanisms

mRNA in eukaryotic cells is packaged into highly compacted ribonucleoprotein particles (mRNPs) in the nucleus and exported to the cytoplasm for translation. mRNP packaging and export require the evolutionarily conserved transcription-export (TREX) complex. TREX facilitates loading of various RNA-binding proteins on mRNA through the action of its DDX39B subunit. SARNP (Tho1 [transcriptional defect of Hpr1 by overexpression 1] in yeast) is shown to interact with DDX39B and affect mRNA export. The molecular mechanism of how SARNP recognizes DDX39B and functions in mRNP assembly is unclear. Here, we determine the crystal structure of a Tho1/DDX39B/RNA complex, revealing a multivalent interaction mediated by tandem DDX39B interacting motifs in SARNP/Tho1. The high-order complex of SARNP and DDX39B is evolutionarily conserved, and human SARNP can engage with five DDX39B molecules. RNA sequencing (RNA-seq) from SARNP knockdown cells shows the most affected RNAs in export are GC rich. Our work suggests the role of the high-order SARNP/DDX39B/RNA complex in mRNP assembly and export.